Colorectal cancer (CRC) is the third most common cancer diagnosed. Although mortality due to CRC has been declining in recent decades, it is the third leading cause of cancer-related deaths in men and women in the US and the fourth leading cause globally. Given these statistics, understanding risk factors for CRC development and mortality remains a top priority. One risk factor associated with increased development of CRC is excess adiposity, or fat; however, much less is known about the relationship between body weight and CRC survival.
Body mass index (BMI) is a commonly used proxy for degree of adiposity, with categories defined as underweight, normal, overweight, and obese. Previous studies demonstrated that BMI status prior to CRC diagnosis is significantly associated with overall mortality, with obesity increasing the risk of mortality as compared to normal weight. In contrast, BMI status in the short-term period following CRC diagnosis was not associated with mortality (1). In addition, work from Fred Hutch Public Health Sciences researchers revealed that the relationship between pre-diagnosis BMI category and survival after CRC diagnosis varies depending on the CRC stage at the time of diagnosis (2). Taken together, the work from these studies and others clearly demonstrated that BMI status prior to CRC diagnosis is associated with survival.
Drawbacks of the previous work in this field are that BMI was typically assessed at only one time point and that the assessment was usually conducted either in the pre-diagnosis or short-term (two years or less) post-diagnosis period. These are limitations because weight loss frequently accompanies CRC, and the change in body weight post-diagnosis may be an important factor in long-term CRC survival. Fred Hutch investigators followed-up the previous work to address this gap, and results from a recent study lead by Dr. Jonathan Kocarnik and colleagues in Dr. Polly Newcomb’s research group in Public Health Sciences Division, provide new insight on the relationship between changes in body weight or BMI and long-term survival after CRC diagnosis.
Dr. Kocarnik and colleagues analyzed data collected from 2,049 participants of the international Colon Cancer Family Registry (3). Self-reported weight and height at baseline (up to two years prior to CRC diagnosis) and at five years post-diagnosis were used to determine long-term change in BMI category and body weight. The authors then assessed the relationship between those measures and long-term survival, with an additional median survival follow-up time of nearly five years. The study showed that weight loss during the five-year period after CRC diagnosis was consistently associated with higher risk of mortality, both overall and CRC-specific death. These trends persisted whether the data were modeled continuously or categorically, or by absolute or percent change in body weight. There was no association for weight gain with long-term survival.
The finding that weight loss, even among overweight and obese individuals (see figure), is associated with lower survival may be particularly important because “these findings are at odds with current guidelines, which suggest that cancer survivors should obtain and maintain a healthy weight. While obesity is certainly a risk factor for the development of colorectal cancer, increasing evidence suggests that the story is not so simple once cancer has developed--in fact, some increased adiposity may actually be associated with increased survival within this context,” as explained by Dr. Kocarnik.
When asked about the next steps to follow-up on this work, Dr. Kocarnik indicated that “Future research is needed to replicate and expand these findings, and especially to account for whether the weight change was intentional or not. It would also be particularly useful to evaluate body composition in addition to weight, and explore how diet and exercise might impact these associations.” Dr. Kocarnik also commented on the tremendous value of the Colorectal Cancer Family Registry as a research resource, and that “weight change is only one of many factors that have been assessed over time, so further analyses within these data will likely uncover additional associations with long-term colorectal cancer survival. Such research is vital for helping cancer survivors live longer, healthier lives.”
Also contributing to this project from the Fred Hutch were Xinwei Hua, Jamaica Robinson, and Drs. Sheetal Hardikar, John Potter, Stacey Cohen, and Amanda Phipps.
Kocarnik JM, Hua X, Hardikar S, Robinson J, Lindor N, Win AK, Hopper JL, Figueiredo JC, Potter JD, Campbell PT, Gallinger S, Cotterchio M, Adams SV, Cohen SA, Phipps AI, Newcomb PA. 2017. Long-term weight loss after colorectal cancer diagnosis is associated with lower survival: the colon cancer family registry. Cancer. doi: 10.1002/cncr.30932.
1. Campbell PT, Newton CC, Dehal AN, et al. 2012. Impact of body mass index on survival after colorectal cancer diagnosis: the cancer prevention study-II nutrition cohort. J Clin Onc. 30:42-52.
2. Kocarnik JM, Chan AT, Slattery ML, et al. 2016. Relationship of prediagnostic body mass index with survival after colorectal cancer: stage-specific associations. Int J Cancer. 139:1065-1072.
3. Newcomb PA, Baron J, Cotterchio M, et al., Colon Cancer Family Registry. 2007. Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer. Cancer Epidemiol Biomarkers Prev. 16:2331-2343.
Funding for this study was provided by the National Institutes of Health, and through cooperative agreements with the following centers: the Australasian Colorectal Cancer Family Registry, the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies, the Ontario Familial Colorectal Cancer Registry, and the Seattle Colorectal Cancer Family Registry.